1998 Fiscal Year Final Research Report Summary
Working mechanism of Ca^<2+>/calmodulin-dependent protein kinase II in synaptic plasticity
| Project/Area Number |
09670096
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General pharmacology
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| Research Institution | Kumamoto University |
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Principal Investigator |
FUKUNAGA Kohji Kumamoto University School of Medicine, Pharmacology, Associate Professor, 医学部, 助教授 (90136721)
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| Co-Investigator(Kenkyū-buntansha) |
KASAHARA Jiro Kumamoto University School of Medicine, Pharmacology, Instructor, 医学部, 助手 (10295131)
YAMAMOTO Hideyuki Kumamoto University School of Medicine, Pharmacology, Assistant Professor, 医学部, 講師 (60191433)
MIYAMOTO Eishichi Kumamoto University School of Medicine, Pharmacology, Professor, 医学部, 教授 (50109659)
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| Project Period (FY) |
1997 – 1998
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| Keywords | CaM kinase II / autophosphorylation / hippocampus / synaptic plasticity / long-term potentiation / NMDA receptor / CA1 / protein phosphatase 2A |
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| Research Abstract |
The observation that autophosphorylation of threonine at position 286 (Thr-286) in Ca^<2+>/calmodulin-dependent protein kinase II (CaM kinase II) converts it from the Ca^<2+>-dependent form to the Ca^<2+>-independent form (constitutively active form) have led to hypothesis that the formation of Ca^<2+>-independent form of the enzyme could encode the frequency of synaptic usage and serve as a molecular switch of "memory". Indeed, induction of long-term potentiation (LTP) in CA1 region of hippocampal slices was associated with long-lasting increases in Ca^<2+>-independent and total activities of CaM kinase IL as well as an increase in the autophosphorylation. We further confirmed with a specific antibody recognized the autophosphorylation of Thr-286 that high, but not low frequency stimulation applied to CA1 afferents resulted in increases in immunofluorescent intensity in the cell bodies and dendrites in the CA1 neurons after LTP induction. The strong immunoreactivities with the anti-ph
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ospho-specific antibody were co-localized with immunoreactivities against NMDA receptor in the CA1 regions. Since the Ca^<2+>-independent activity can be reversed by protein phosphatases, we next investigated regulation of protein phosphatase activity during LTP induction. A significant decrease in protein phosphatase 2A activity in the soluble fractions was observed in the CA1 regions following LTP induction without change in protein phosphatase 2C activity using autophosphorylated CaM kinase II as substrate. In vitro and in vivo studies revealed that phosphorylation of B'alpha subunit, a regulatory subunit of protein phosphatase 2A, by CaM kinase II is underlying the inhibition of the protein phosphatase activity during LTP induction. These results suggest that the decreased protein phosphatase 2A activity by CaM kiriase II can synergistically contribute to the expression of LTP by favoring generation of the constitutively active CaM kinase II and by regulating the phosphorylation of specific synaptic proteins. Less
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Research Products
(30 results)
